Sam and Dean Winchester have caught a lot of lucky breaks over the years on Supernatural, including an angel on their side and the FBI off their case. But that's all ending in season seven, according to the show's producers and stars.

Spoilers ahead...

Talking to reporters at San Diego Comic-Con, the stars of Supernatural and producer Ben Edlund said that life will be a lot tougher for the Winchesters in season in general.

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As Jared Padalecki observed, there have been a lot of questions over the years about how the Winchesters say ahead the of the law, how they keep using fake credit cards without getting caught, and how they're not on FBI databases. And that will all come to a head this season — they will be on the run like never before. He joked that they'll be like Thelma and Louise — or maybe Butch and Sundance.

And they don't have the resources and loopholes they used to have at their disposal. Sam is off the demon blood for good, and they can no longer call on the angel Castiel to get them out of a jam. Their only resources are their own wits and their determination.

And meanwhile, star Jensen Ackles said, the brothers will be up against a huge evil that is not in any lore. Sam, Dean and Bobby will be having a harder time than ever figuring out what to do about this unknowable, unstoppable evil force. (And it sounds like Bobby will be doing a lot more traveling with the boys and be a lot more present in several episodes, judging from Jim Beaver's comments.)

In the actual Supernatural panel in Hall H, they showed a clip from the first episode filmed, which Ackles directed — in which we see a flashback to Sam's childhood including his first ever kiss. And the words "Amy Pond" are mentioned. And it's framed by a scene of Sam and that girl as adults — the girl being played by Firefly's Jewel Staite!

And producer Sera Gamble revealed that fan favorite Jo, who apparently died in season five, will be back again this year. Also, Castiel will definitely be in the first two episodes of the season, but Gamble wouldn't say much beyond that. Also, we see Crowley (Mark Sheppard) very early on — Castiel has big plans for Crowley, and we learn what they are pretty quickly.

And before everything "goes to Hell completely" for Castiel, we get to see him playing god, says Gamble. Also, Misha Collins hinted that we'll see an unexpected parallel between Castiel and the Antichrist in the season opener.

And Jim Beaver told the panel that he suspects we haven't seen the last of Sheriff Mills — and hinted that she might be a full-blown love interest for Bobby, whose love life has not gone well in the past.

Ben Edlund told the panel he's not sure how they could possibly get more meta than last season's "The French Mistake." But in the pressroom, he told reporters he really wants to get the Winchester Brothers on a spaceship — preferably something that looks like an unofficial continuation of the late 1970s Buck Rogers in the 25th Century show. He figures there are enough reality-warping demons on the show to make that entirely possible.

The panel ended with a sneak peek of the gag reel from the Season 6 box set, featuring lots of Jensen and Jared dancing around, flubbing their lines, and generally acting ridiculous (and awesome.) And at one point, the brothers dare Misha Collins to eat a worm, but he wears it instead, as a "worm-stache."